The Biomarkers Core is a unique resource for the University of Minnesota TTURC. Members of this Core have extensive experience in the quantitation of nicotine metabolites and carcinogen biomarkers, and expertise in phenotyping and genotyping methods. They have developed biomarker methods which are now widely used to assess tobacco harm reduction approaches. The Biomarkers Core carded out nearly 11,000 analyses of urinary metabolites in the past 4 years of this TTURC and has contributed significantly to TTURC research conclusions. In the present proposal, the Biomarkers Core will perform analyses of the following: nicotine metabolites in blood and urine; total cotinine in blood and urine; anatabine in urine; r-1,t-2,3,c-4- tetrahydroxy- 1,2,3,4-tetrahydrophenanthrene in blood and urine, 1-hydroxypyrene in urine; trans, trans-muconic acid in urine; mercapturic acids of acrolein and butadiene in urine; anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-hemoglobin adducts, ethylene oxide-hemoglobin adducts, and hemoglobin adducts of ethylating agents. In addition, genotyping for polymorphisms in the nicotine metabolizing enzyme CYP2B6 will be carried out. A seamless communication mechanism with TTURC researchers and the Design and Analysis Core has been developed over the past 4 years and will be continued. The Biomarkers Core will provide critically important data, particularly for TTURC Projects 1 and 3, and these data will be essential in evaluating the relationship of harm reduction approaches to tobacco-related cancer.